The invention relates generally to a composition of non-radioactive traceable metal isotope-enriched nanoparticles, and methods of their use for determining in-vivo biodistribution. One or more of the embodiments relate to non-radioactive traceable metal isotope-enriched superparamagnetic iron oxide (SPIO) nanoparticle composition and methods of their use for determining in-vivo biodistribution.
Superparamagnetic iron oxide (SPIO) nanoparticles of 10 to 1000 nm diameter are used as contrast agents to increase proton relaxation times in tissue following injection into patients to provide contrast enhancement in magnetic resonance imaging (MRI). It is often necessary to determine the nature of distribution of the contrast agent within the body. These determinations require detailed pharmacokinetic knowledge of the biodistribution and clearance of the contrast agent in animals, as well as blood and plasma clearance in human.
Although the degree of contrast observed by MRI depends upon the amount of contrast agent in a given tissue, it is generally not possible to quantitiatively determine the absolute concentration of conventional SPIO agents in a tissue. This is in part because of the effects of the SPIO agent on proton relaxation times. The SPIO agent's relaxivity properties may vary by interactions with proteins, cells or other components of the body and by possible metabolism or degradation of the SPIO agent within the body. Additionally, at lower concentrations of the SPIO agents, imaging sensitivity associated with MRI is a further barrier to quantitatively determine the concentration of the SPIO agents in tissue.
Other methods for determining SPIO concentrations in-vivo include iron-sensitive dyes, fluorescent/radioactive reporter labels, and quantitative elemental analysis. Qualitative methods, to determine SPIO distribution in tissue, rely on treating tissue specimens with iron staining agents, and cannot quantitatively determine biodistribution of the SPIO-based injected agents. Moreover, iron staining dyes do not necessarily distinguish between endogenous iron and SPIO nanoparticle associated iron. Dye, fluorophore, radioactive or other labels conjugated to the agent, change the composition of the SPIO particle, and may therefore alter its in-vivo performance. Furthermore, the label may not remain associated with the SPIO in-vivo, and thus tracking the label may not accurately reflect the distribution of the SPIO particle itself. In human studies, the potential risk of exposure to radioactive materials is also another concern. Elemental analysis of tissue samples to determine iron concentration could be achieved, however, with conventional SPIO agents, there is no way to distinguish between endogenous iron and SPIO-associated iron in the same tissue samples.
Therefore, there is a need for a label-free, non-radioactive method to quantitatively measure the in-vivo biodistribution of the injected nanoparticles such as SPIO nanoparticles.